This project is one of three proposals that uses the Interactive Research Project Grant mechanism to determine if inhibitors of polyamine metabolism can be used to prevent colon cancer in humans. The intermediate-term objective will be to prevent recurrence of adenomatous polyps, a surrogate for colo-rectal cancer. The specific aims of the current proposal are: 1) to measure the effects of chronic low dose difluoromethylornithine (DFMO) on polyamine levels in rectal mucosal tissues, and 2) to determine the effect of low dose DFMO on audiometric-measured hearing. In a short-term phase IIa trial, participants have received different doses of oral DFMO for one month and the effect on polyamine synthesis in rectal mucosal biopsies measured. Based on this data we have designed a longer term (one year) phase IIb trial in which four groups of 25 participants each will be randomized to receive either oral placebo, DFMO (low dose), DFMO (intermediate dose), and DFMO (high dose) for one year. The following parameters will be measured serially: formal audiometry, and polyamine content in rectal mucosal biopsies. Biochemical parameters and clinical side effects will also be monitored. Data management and analysis will be thorough and detailed. The results from this trial should allow us to accurately determine the dose of DFMO that will reduce polyamine content and produce little to no side effects. Subsequently, this dose of DFMO would be used in a future investigation: a randomized phase Ill trial in which the effect of DFMO on reducing colon polyp recurrence would be measured.